Interpretive Summary: Marek's disease (MD) is an economically-important disease of chickens caused by a pathogenic virus. Currently, vaccines have controlled the problem but new emerging viral strains that vaccines cannot control are being encountered more frequently. To help combat MD, chickens are being selected for genetic resistance, which augments vaccinal control measures. Biotechnology may greatly enhance the rate of poultry breeding improvement by identifying the genes responsible for conferring resistance. One way to identify these genes is to capitalize on MD virus-chicken protein-protein interactions. As a result of our experiments, genetic markers to these genes can be used to generate more disease-resistant chickens. Furthermore, the identification of these genes provides insights on what immune responses help fight the disease. Ultimately, consumers will benefit as losses due to disease are reduced.

Technical Abstract:
Genetic resistance to Marek's disease (MD) has been proposed as a method to augment current vaccinal control of MD. While it is possible to identify quantitative trait loci (QTL) and candidate genes that are associated with MD resistance, it is necessary to integrate functional screens with linkage analysis to confirm the identity of true MD resistance genes. To help achieve this objective, a comprehensive two-hybrid screen was conducted using genes unique to virulent Marek's disease virus (MDV) strains. Potential MDV-host protein interactions were tested by an in vitro binding assay to confirm the initial two-hybrid results. As a result, six new MDV-chicken protein interactions were identified and include the chicken proteins MHC class II ' and invariant (Ii) chain, growth-related translationally-controlled tumor protein (TPT1), complement component C1q-binding protein (C1QBP), and retinoblastoma-binding protein 4 (RBBP4). Mapping of the encoding chicken genes suggests that BLB, the gene for MHC class II ' chain, is a positional candidate gene. In addition, the known functions of the chicken proteins suggest mechanisms that MDV might utilize to evade the chicken immune system and alter host gene regulation. Taken together, our results indicate that integrated genomic methods provide a powerful strategy to gain insights on complex biological processes, and yield a manageable number of genes and pathways for further characterization.